Objectives COVID-19 survivors are reporting residual abnormalities after discharge from the hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. The aim of this study was to describe lung function and to identify biomarkers in serum and induced sputum samples from patients recovering from COVID-19 hospitalisation. Methods Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalisation. Patients’ epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardised 6-minute walk test (6 MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. Results A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% (47/100) of patients. CT was normal in 48% (48/100) of patients. Lung function was normal (FEV1 ≥80%, FVC ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide [DLCO] ≥80%) in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p <0.0001) and a lower serum LDH level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 during hospital stay. Conclusions A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases.

Background The coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. Methods Post-hoc analysis of the international, multicentre, “real-world” HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65–74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. Results 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71–83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P &lt; 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8,06), peripheral oxygen saturation at admission &lt;92% (OR 5.85), severe lymphopenia (&lt;500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) &gt;1 (OR 8.31) to be independent predictors of mortality. Conclusion Patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation &lt;92%, severe lymphopenia and qSOFA scale &gt;1 were independent predictors of mortality in this population.

Objective Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. Methods Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 μg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. Results Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104–335) and 331 (140–476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. Conclusion Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.

Dalbavancin (DAL) is a lipoglycopeptide with bactericidal activity against a very wide range of Gram-positive microorganisms. It also has unique pharmacokinetic properties, namely a prolonged half-life (around 181 h), which allows a convenient weekly dosing regimen, and good diffusion in bone tissue. These features have led to off-label use of dalbavancin in the setting of bone and joint infection, including prosthetic joint infections (PJI). In this narrative review, we go over the pharmacokinetic and pharmacodynamic characteristics of DAL, along with published in vitro and in vivo experimental models evaluating its activity against biofilm-embedded bacteria. We also examine published experience of osteoarticular infection with special attention to DAL and PJI.

Introduction A growing evidence suggests that immune dysregulation and thrombotic phenomena are key features in the pathophysiology of COVID-19. Apart from antivirals and respiratory support, anticoagulants, corticoids and immunomodulators are increasingly being prescribed, especially for more severe cases. We describe the clinical outcome of a large cohort of patients preferentially treated with glucocorticoids and interleukin inhibitors. Methods Single center and retrospective case series. Adult patients admitted with COVID-19 related respiratory insufficiency were included.Patients who died within 2 days after admission and those testing positive but asymptomatic were excluded. We defined two study periods: from March 3rd to March 31 st, 2020 (beginning of epidemic until peak of incidence) and April 1 st to May 7 th,2020 (second half of epidemic). The majority of patients received respiratory support,combinations of antimicrobials, anticoagulants, corticoids and interleukin inhibitors.Antivirals were preferentially given in the first period. The clinical outcome (death and ventilator dependency) of both periods was compared. Results From March 3 rd to May 7 th, 685 patients were included for analysis (58.4% males, mean age 68.9 years). Patients in the first period (n=408) were younger (66.6 vs 71.1 years, p=0.003),presented lower mean P a O 2/F i O2 ratio at admission (256.5 vs 270.4 mm Hg,p=0.0563), higher ferritin (1520 vs 1221 ng/ml, p=0.01), higher IL-6 (679 vs 194 pg/ml,p<0.0001) and similar D-dimer levels (3.59 vs 3.39 μg/mL, p=0.65) compared to the second period (n=277). Lopinavir/ritonavir and interferon were preferentially given in the first period (23.8% and 32% vs 1.8% and 11.9%, p<0.0001). Use of corticoids (88.2% vs 87.4%, p=0,74) and tocilizumab (26.29 vs 20.22% p=0.06) were similarly administered in both periods. Patients in the second period needed less mechanical ventilation (4.9% vs 16.9%, p<0.0001), fewer ICU admission (6.1% vs 20.1%,p<0.0001) and showed similar mortality (17.7% vs 15.4%, p=0.43). Infectious and thrombotic complications were comparable in both periods (both around 8%, with no statistical difference). Patients treated with tocilizumab (n=163) had lower mortality rate compared to those untreated under the same indication (7.9% vs 24.2%, p<0.0001).Conclusions In this large retrospective COVID-19 in-hospital cohort, lopinavir/ritonavir and interferon showed no significant impact on survival. Extensive use of corticosteroids and tocilizumab resulted in good overall outcome and showed acceptable complication rates.